Abstract
BackgroundSevere malaria anaemia in the semi-immune individuals in the holo-endemic area has been observed to occur at low parasite density with individual variation in the responses. Thus the following has been thought to be involved: auto-immune-mediated mechanisms of uninfected red blood cell destruction, and host genetic factors to explain the differences in individual responses under the same malaria transmission. In this study, the extent of red blood cell (RBC) destruction in different strains of semi-immune mice model at relatively low parasitaemia was studied.MethodologyTo generate semi-immunity, four strains of mice were taken through several cycles of infection and treatment. By means of immunofluorescent assay and ELISA, sera were screened for anti-erythrocyte auto-antibodies, and their relationship with haematological parameters and parasitaemia in the strains of semi-immune mice was investigated.ResultsUpon challenge with Plasmodium berghei ANKA after generating semi-immune status, different mean percentage haemoglobin (Hb) drop was observed in the mice strains (Balb/c = 47.1%; NZW = 30.05%; C57BL/6 = 28.44%; CBA = 25.1%), which occurred on different days for each strain (for Balb/c, mean period = 13.6 days; for C57BL/6, NZW, and CBA mean period = 10.6, 10.8, 10.9 days respectively). Binding of antibody to white ghost RBCs was observed in sera of the four strains of semi-immune mice by immunofluorescence. Mean percentage Hb drop per parasitaemia was highest in Balb/c (73.6), followed by C57BL/6 (8.6), CBA (6.9) and NZW (4.0), p = 0.0005. Consequently, auto-antibodies level to ghost RBC were correlated with degree of anaemia and were highest in Balb/c, when compared with the other strains, p < 0.001.ConclusionThe results presented in this study seem to indicate that anti-RBC auto-antibodies may be involved in the destruction of uninfected RBC in semi-immune mice at relatively low parasite burden. Host genetic factors may also influence the outcome of auto-immune mediated destruction of RBC due to the variation in Hb loss per % parasitaemia and differences in antibody titer for each semi-immune mice strain. However, further studies at the molecular level ought to be carried out to confirm this.
Highlights
Severe malaria anaemia in the semi-immune individuals in the holo-endemic area has been observed to occur at low parasite density with individual variation in the responses
Parasitaemia-time course, profile of severe malaria anaemia and erythropoietic response in the semi-immune mice strains Four strains of mice (Balb/c, B6, New Zealand White (NZW) and CBA) were taken through several cycles of infection with 104 P. berghei ANKA followed by pyrimethamine and chloroquine treatment to generate semi-immune status
Upon challenge with 104 P. berghei ANKA after generating semiimmune status, similar parasitaemia profiles were observed in different cycles of infection in the same strain, but different responses were observed in the strains (Figure 2)
Summary
Severe malaria anaemia in the semi-immune individuals in the holo-endemic area has been observed to occur at low parasite density with individual variation in the responses. The following has been thought to be involved: auto-immune-mediated mechanisms of uninfected red blood cell destruction, and host genetic factors to explain the differences in individual responses under the same malaria transmission. The extent of red blood cell (RBC) destruction in different strains of semi-immune mice model at relatively low parasitaemia was studied. Central to the proposal to explain the pathogenesis of SMA is the destruction of high numbers of uninfected red blood cells (uRBC) compared with the infected RBC (iRBC) [4], due to the consistent observation of SMA at relatively low parasite burdens of semi-immune individuals in malaria endemic areas [5]. Inadequate reticulocyte response has been proposed as being a contributory factor to the SMA, due to an abnormal bone marrow cellularity reflected by low reticulocyte counts in SMA patient [7]
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